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- Cellular and molecular mechanisms of toxicity of ingested nanomaterialsPublication . Gramacho, Ana Catarina; Rolo, Dora; Martins, Carla; Assunção, Ricardo; Gonçalves, Lídia M.; Bettencourt, Ana; Alvito, Paula; Pereira, Joana; Jordan, Peter; Silva, Maria João; Louro, HenriquetaThe technology based on manufactured nanomaterials (NMs) has been pointed as key enabling technology, due to its potential to improve many products and processes, namely in agriculture, food and feed industry. Many of such products, already available, have NMs such as titanium dioxide nanomaterials (TiO2) and the oral exposure may occur either directly, through the consumption of products/pharmaceuticals containing NMs, or indirectly, through the ingestion of foods contaminated with NMs released from food-contact materials or even through concentration in the food chain due to environmental accumulation. Therefore, the gastrointestinal tract (GIT) appears to be a probable route of exposure to NMs and may lead to systemic exposure if the body barriers are surpassed. One major concern for public health is that NMs may produce adverse outcomes (AO) such as genotoxic effects that are associated with increased risk of cancer. Although NMs have been extensively investigated in recent years, the studies have generated contradictory results, possibly due to differences in the physicochemical properties of the NMs studied and to other variables in the test systems. INSA has previously shown that NMs with the same chemistry, but differing in primary properties may yield different biological effects. Conversely, the NMs properties are context-dependent, i.e. can be affected by the surrounding matrix. These secondary features may be potentially more relevant for determining toxicological outcomes. In particular, processes like digestion may modify the NMs characteristics leading to unexpected toxicity in intestine cells. INGESTnano project aims to investigate the nano-bio interactions of NMs, at cellular and molecular level, in the context of intestinal tract and digestion processes, to better understand their potential negative impacts on human health with special reference to organ-specific cells. TiO2 has been selected as case-study to setup a workflow for addressing nanosafety concerns that may be in the future applied to other NMs to which GIT may be exposed. It is expected that this project will contribute to the safety evaluation of the TiO2 ingested, by elucidating key events (KE) elicited by these NMs and linking exposure to AO.
- Adverse Outcome Pathways (AOPs) development, a tool for predictive nanotoxicologyPublication . Rolo, Dora; Louro, HenriquetaNanomaterials (NMs) have the potential to improve novel and useful wide applications in electronics, chemicals, environmental protection, biological medicine, food and others. Therefore, NMs rapid proliferation presents a dilemma to regulators regarding hazard identification, with increased concerns for public health. Predictive nanotoxicology describes a multidisciplinary approach to NMs evaluation that uses a set of in vitro and in silico methods to forecast the effects on biological systems. This approach offers advantages to traditional hazard assessment methods, such as reducing the reliance on animal studies, associated costs and ethical issues. It may be used with several applications in environmental and human health risk assessment and NMs hazard identification, as well as for regulation. The Adverse Outcome Pathways (AOPs) are the central element of a toxicological knowledge framework, promoted by member countries through OECD, built to support chemical risk assessment based on mechanistic reasoning. AOPs describes a logical sequence of causally linked events at different levels of biological organisation, which follows exposure and leads to an adverse health effect in humans or wildlife. The integrative analysis of the cellular and molecular mechanisms of nanotoxicity towards a definition of key events, may lead to adverse outcomes, driving a sequential line and defining an AOP landscape. Each defined AOP is available for crossing data, linking known and unknown landscapes. Since the biological effects that relate to possible genotoxicity and increased risk of cancer due to NMs exposure are under analysis, the development and assessment of AOPs are important novel strategic tools for predictive nanotoxicology.